Chuan Xin Lian

Thirty-three randomised controlled trials with 7,175 participants. A. paniculata improved cough (standardised mean difference -0.39, 95% CI -0.67 to -0.10) and sore throat (SMD -1.13, 95% CI -1.37 to -0.89) against comparators. No major adverse events were reported and the minor ones were mainly gastrointestinal.

The authors judged the methodological quality generally poor, and noted that the trials seldom reported manufacturing or quality-control details for the herbal material, which limits how far a given commercial product inherits this evidence. A correction to this paper was published in PLOS ONE in November 2018; it is a correction, not a retraction.

Ten randomised controlled trials and three intensive-monitoring studies of oral A. paniculata monotherapy in upper respiratory tract infection, non-infective diarrhoea and autoimmune disease, searched across six databases to August 2018. The pooled incidence of serious adverse events from the RCTs was 0.02 per 1,000 patients (95% CI 0.0 to 0.5), that is, very rare.

This is the best available quantification of the oral herb's safety, and it should be read alongside the separate and much less reassuring record of the injectable andrographolide derivatives.

262 clinical studies were reviewed. Among 9,490 users of andrographolide injections, 383 (4.04%) reported adverse drug reactions; the three most-used injections had ADR incidences of 5.48%, 3.69% and 5.33%. Fifty-five patients experienced life-threatening anaphylactic shock and three died. By contrast, nine herbal preparations of the whole plant produced mainly mild-to-moderate gastrointestinal and skin reactions that resolved on withdrawal.

The conclusion is a clean separation: the parenteral derivative requires caution, the oral herbal preparation is essentially safe.

Double-blind trial in 224 patients with mildly to moderately active ulcerative colitis, randomised to HMPL-004 at two doses or placebo for eight weeks. At week 8, 60% of those on 1,800 mg daily were in clinical response against 40% on placebo; clinical remission was 38% versus 25%. Adverse events were comparable across arms (60% placebo, 53-60% treatment).

This is the strongest randomised evidence for A. paniculata outside respiratory infection, and it establishes the extract as an active immunomodulator at gram-level daily doses.

165 hospitalised patients with asymptomatic-to-mild COVID-19 completed this prospective double-blind placebo-controlled trial (83 extract, 82 placebo), receiving 180 mg/day of andrographolide for five days. The extract did not reduce disease progression, the primary question. It did significantly relieve headache on day 1 and speed recovery from olfactory loss.

Mild diarrhoea was the commonest adverse event (13.3% versus 7.3% on placebo) and resolved within days; no hepatic or renal toxicity was detected. A useful negative trial: it does not support A. paniculata as an antiviral for COVID-19.

Andrographolide dosed to albino rats produced structural damage to the testis and to spermatozoa in the cauda epididymidis, characterised by the authors as a male antifertility property.

This is the anchor study for the male-fertility signal. It is a rodent study at doses not directly translatable to a human course, and other rodent work at 20-1,000 mg/kg for 60 days found no testicular toxicity, so the signal is real but unresolved.